# High-Throughput Functional Genomics of Variants in Genes Linked to Substance Use Disorders

> **NIH NIH DP1** · WASHINGTON UNIVERSITY · 2024 · $466,500

## Abstract

ABSTRACT
High-throughput functional genomics of variants in genes linked to substance use disorders
Understanding of the genetic basis of substance use disorders has advanced significantly in the recent past; the
generation of a reference human sequence in the early 2000’s enabled Genome Wide Association Studies
(GWAS), which in turn led to the identification of thousands of genetic variants that are statistically significantly
associated with substance use and substance use disorders. The number of these clinically relevant variants
continues to grow proportionally with the increase in sample sizes for GWAS and genome sequencing studies
of substance use disorders. Model organism studies have also led to the identification of genes and pathways
that are linked to these phenotypes. However, one persistent bottleneck in this field has been the lack of
experimental testing of nearly all (>99%) of these variants in genes and regulatory regions to determine
which are functionally significant. Determining the functional effects of genetic variants is crucial to acquiring
a molecular understanding of the basis of substance use disorders, and this deeper understanding will enable
future development and testing of targeted and rationally designed therapeutic interventions. This forward-
thinking application proposes to address this gap by applying highly innovative high-throughput
functional genomics approaches, including Massively Parallel Reporter Assays (MPRAs) and Deep
Mutational Scan (DMS) techniques, that were recently deployed for the study of rare Mendelian
disorders, to the study thousands of both noncoding and coding variants associated with substance
use disorders. These approaches have not previously been applied to the genetics of substance use disorders,
although they have enabled significant advancements in other fields, such as the genetics of
neurodevelopmental and neuropsychiatric disorders. Furthermore, this early-stage investigator’s
multidisciplinary training, including MD/PhD degrees, Pediatrics residency, a postdoctoral fellowship, and four
years of dedicated K08 Early Career Development work that was focused on acquiring expertise in the use of
functional genomics techniques, has established him as a rising leader in the field of human genetics. His prior
paradigm-altering and team-based accomplishments include establishment of an exome sequencing testing
pipeline for children with autism in 2015, ongoing coordination of the Model Organism Screening Center for the
NIH-funded Undiagnosed Diseases Network, and leadership of a $1.5 million institutionally-funded, multi-
investigator functional genomics project that resulted in deployment of critical infrastructure and delivered a 10:1
return on investment in subsequent grant funding. Although this talented investigator has not previously focused
on substance use disorders, he has established a collaboration with a world expert in this field, Dr. Laura Bierut,
who has agreed to advise ...

## Key facts

- **NIH application ID:** 10895531
- **Project number:** 5DP1DA058706-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Dustin M Baldridge
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $466,500
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10895531

## Citation

> US National Institutes of Health, RePORTER application 10895531, High-Throughput Functional Genomics of Variants in Genes Linked to Substance Use Disorders (5DP1DA058706-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10895531. Licensed CC0.

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